Ketamine for Depression

Ketamine has 9.1x higher odds vs placebo of a clinical response for depression at 24 h, 6.8x at 3 days, and 4.9x at 7 days, from a single dose. [1]
What if there was a depression treatment that was largely unknown, solely because it was no longer patentable, and therefore no drug companies want to promote it?

Does it work?

It seems that Ketamine has a significant, but short-lived benefit for treating depression.
"For single infusion studies, effect sizes were large and significant at 4 h, 24 h and 7 days."[2]"Overall, depression scores were significantly decreased in the Ketamine groups compared to those in the control groups (SMD = -0.99; 95 % CI -1.23, -0.75; p [3] (For context, an SMD of 0.2 is small, >0.5 is medium, and >0.8 is large. This is 0.99!)

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Is this illegal?

No — you can go to a doctor or medical clinic and have prescription Ketamine treatments. Ketamine is approved by the FDA as an anaesthetic. There are many legal Ketamine clinics that use prescription Ketamine. They are generally expensive.

What does the research show?

IV (intravenous, into veins) KetamineResults: "For single infusion studies, effect sizes were large and significant at 4 h, 24 h and 7 days."[2]Dosage: 0.5 mg/kg typically.
Regimen: Most research uses either a single dose, or 6 doses over two weeks (Mon-Wed-Fri x2).

Oral KetamineHow it was taken: Ketamine was swallowed in a syrup, nightly for 28 days.
Dosage: up to 0.5 mg/kg per night.
Results: Significant response by day 3 for anxiety, and day 14 for depression.[4]

Why isn't this yet a widespread treatment?Because Ketamine for depression is still in Phase 2 trials with the FDA. However the FDA has granted "breakthrough therapy status" to esKetamine (on August 16, 2016), which would speed the approval process for depression.

Why is Ketamine still in Phase 2 trials?Ketamine's patent has expired. This means drug companies will find it difficult to make lots of money from selling it, compared to other patentable drugs. The government funds Phase 2 research for Ketamine via grants, however the cost of a Phase 3 trial is so high that government grants are not sufficient to fund this work. There are only two paths for Ketamine being FDA approved for depression: a) a drug company develops a similar drug that works the same way as Ketamine, but is different enough that they can patent it and make lots of money (this is what is happening with esKetamine) or b) a wealthy individual funds the Ketamine Phase 3 trials out of the goodness of their own heart.

What protocols and dosages are used in research?Almost all use 0.5-mg/kg dosages. Most studies are done intravenously. Some studies do Monday-Wednesday-Friday infusions.

Is there research on oral Ketamine, instead of nasal or IV?One study used 0.5-mg/kg daily and found significant improvement in both depressive symptoms and symptoms of anxiety in all eight subjects. Dosage was daily. Depression symptoms improved significantly by day 14 until the end (day 28), and anxiey symptoms improved significantly by day 3 until the end (day 28). "The response rate for depression is similar to those found with IV Ketamine; however, the time to response is more protracted." — basically, it worked similarly well for depression as IV Ketamine, though took longer to take effect.[4]

What are the side effects?"None of the studies included in the current meta-analysis documented major adverse effects, but side effects such as transient headache, dizziness and nausea were commonly reported; such side effects reportedly dissipated fairly quickly, usually once the infusion was complete."[2]

What are the worst things about this? Why might this not work?"Middle- and long-term efficacy and safety have yet to be explored. Extrapolation should be cautious: Patients included had no history of psychotic episodes and no history of alcohol or substance use disorders, which is not representative of all the depressed patients that may benefit from this therapy."[3] Also, it's important to realize that one dose won't solve your depression forever.

Does Ketamine work for everyone who has depression?No. Seems like it works for around ~70% of people in research so far.[2]

Unfortunately, given that drug companies don't make money from promoting Ketamine (because the patent has expired), there is no marketing budget to tell people that it has this level of effectiveness for depression.

You may or may not want to privately mention this to someone you know who would be interested.

Ketamine as a treatment for depression. Don't ignore it just because big pharma does.